The care of the severely injured patient continues to be a major medical problem in the United States. Despite substantial advances in the successful maintenance of these patients in the period immediately following injury, these patients often die weeks or months later of a syndrome termed multiple organ failure (MOF). The sequence of events that lead to MOF are poorly understood and it is this gap in our knowledge that the proposed studies hope to bridge. It is our hypothesis that MOF results from prolonged activation of components of the host inflammatory systems, especially the leukocyte, and that this activation results in cellular injury of the organs. This application describes experiments that will utilize quantitative biochemical and immunologic techniques to investigate areas that bear directly on issues we believe to be relevant to the pathogenesis of MOF. These are the metabolism of LPS, studies of the biochemistry and physiology of neutrophil function as it relates to cellular injury, and the role of adhesive proteins in regulating cell-cell interactions. These studies will initially be developed with in vitro and in vivo models and then, when appropriate, extended to trauma patients. A part of our long range goals is the development of an effective relationship with the Department of Surgery at the University of Washington so that information derived from the basic studies proposed here can be efficiently transferred to the clinic to improve the care and prognosis of the severely injured patient.